Central hypotensive and antihypertensive activities of imidazolidines, structurally related to clonidine

A central nervous origin of the hypotensive effect of a number of clonidine-like drugs was demonstrated by means of infusions of low doses into the vertebral artery of chloralose-anaesthetized cats. Systemic injections of the same amounts were significantly less effective than after their application via the central route. In addition, pretreatment with the alpha-adrenoceptor blocking agent piperoxan effectively blocked the centrally induced hypotensive response. It is concluded that imidazolidines of the clonidine-type probably display the same mechanism of action as that manifested by clonidine itself. The centrally mediated depressor response was quantified by means of an ED25. The antihypertensive and bradycardic activities of clonidine and a number of its derivatives were quantified by means of ED20 values calculated from dose-response curves following intravenous administration to conscious, spontaneously hypertensive rats. Linear relationships were found between the hypotensive activity in the anaesthetized, normotensive rat, the central hypotensive potency in the anaesthetized cat and the antihypertensive efficacy in the conscious, spontaneously hypertensive rat. These findings indicate a similarity between central alpha-adrenoceptors in these different animal species.